The immunohistochemical expression and potential prognostic value of HDAC6 and AR in invasive breast cancer

Hum Pathol. 2018 May:75:16-25. doi: 10.1016/j.humpath.2017.11.010. Epub 2017 Nov 24.

Abstract

Previous studies have investigated the role of histone deacetylase 6 (HDAC6) in the regulation of androgen receptor (AR) in prostate cancer; however, the role of HDAC6 has not yet been clearly identified in breast cancer. The aim of this study was to examine the expression of HDAC6 and AR, determine the correlation between HDAC6 and AR, and assess the prognostic value of HDAC6 and AR in breast cancer. A total of 228 cases of invasive breast cancer were randomly selected. The expression of HDAC6 and AR was analyzed by immunohistochemistry. χ2 Tests were performed to determine the association between conventional clinicopathological factors and HDAC6, AR, and HDAC6/AR co-expression. Spearman correlation methods were performed to determine the correlation between HDAC6 and AR, and Kaplan-Meier analyses were performed to determine the prognostic impact of HDAC6, AR and HDAC6/AR co-expression; 58.8% (134/228) patients exhibited high expression of HDAC6. High HDAC6 expression was significantly associated with high histologic grade (G3) (P<.001) and p53 overexpression (P=.002). HDAC6 and AR expression levels were significantly associated (r=0.382, P<.01). In estrogen receptor (ER)-negative samples, high expression of HDAC6 was more common in the AR+ groups (P<.001) and correlated with high histologic grade (G3) (P=.009), as well as higher HER2 (P=.006) and p53 levels (P=.012). Higher expression of AR and HDAC6 and HDAC6/AR co-expression had a worse clinical prognosis. The expression levels of HDAC6 and AR are correlated in breast cancer; moreover, HDAC6 and AR have prognostic value in predicting the overall survival (OS) of ER-negative breast cancer patients.

Keywords: Androgen receptor; Breast cancer; ER-negative breast cancer; Histone deacetylase 6; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Female
  • Histone Deacetylase 6 / analysis
  • Histone Deacetylase 6 / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Receptors, Androgen / analysis
  • Receptors, Androgen / biosynthesis*

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • Receptors, Androgen
  • HDAC6 protein, human
  • Histone Deacetylase 6